ES2221396T3 - TRICHOLOGICAL LOTION FOR TOPICAL USES. - Google Patents

Abstract

The present invention concern a cosmetic composition for topical application for reactivating the physiological growth of hair, said composition comprising a synergistic association of cysteine, lysine or derivatives thereof, with a glycoprotein, in a physiologically acceptable vehicle.

Description

Trichological lotion for topical uses.

Technical field

The present invention refers to a cosmetic compound for topical application to reactivate the physiological growth of hair in regions affected by hair loss in which there are follicles that have not atrophied completely.

State of the art

Specifically, the present invention makes reference to a cosmetic compound in the form of a lotion that is suitable for topical application to the scalp in order to improve the aesthetic appearance of the hair that is present and make that the hair grows thicker in the areas where the loss of hair caused by androgenic alopecia and / or defluvium has had place.

Lotions and preparations against the fall of hair, based on active ingredients that improve the trophism of scalp and reactivate hair follicles, they are known for a long time.

Currently, commercially prepared available for trichological use, generally include substances rubefacient, vitamin compounds and their derivatives, normally in association with suitable nutritional compounds.

Among the various commercially prepared available, a preparation for the prevention of hair loss based on nicotenil, an association of three active ingredients, Benzyl nicotinate, silanetriol monomethyl methionate and Panthenol has been known since 1989. The topical application of this prepared to the scalp stimulates blood circulation, the which, transporting a surplus of nutrients to the root of hair, reduces and limits hair loss.

In addition, a preparation for the treatment against hair loss has been known since 1991, which is based on the association of three active principles whose activity stimulates hair follicles: lauroyl sodium cysteine, lysine hydrochloride and nicotenil.

Be prepared, when administered locally in the scalp of patients affected by alopecia androgenic, has proven effective in reducing the loss of hair.

Cosmetic preparations of the prior art, although they have been found to be effective in slowing the loss of the hair, have not been proven capable of effectively doing that the hair grows thicker in the treated scalp and produce a visually appreciable increase in the diameter of the Body.

Formulations based on a principle pharmacologically active, minoxidil, are also currently commercially available: minoxidil had been used in the treatment of high blood pressure and it was discovered unexpectedly it was effective in causing the regrowth of hair in subjects affected by androgenic alopecia.

Although the daily and prolonged administration of Minoxidil-based formulations have proven effective in the treatment of various forms of hair loss and stop significantly hair loss, has the disadvantage of provoke in a significant percentage of the treated subjects a variety of side effects, such as skin reactions allergic, hirsutism, drops in blood pressure and pain head.

In the current state of the art, therefore, You feel the need to have new and effective preparations Trichological whose formulations are not based on principles assets that have intense activity from the point of view pharmacological and therefore induce side effects dangerous.

Description of the invention

One of the objectives of the present invention is provide a useful trichological cosmetic compound to reactivate a physiological growth of hair in regions affected by hair loss and produce structural and morphological changes in hair that can be seen from a point of view cosmetic.

Another object of the present invention is to provide a cosmetic compound for local application in leather scalp that slows hair loss and makes it said hair grow thicker, and whose use involves essentially no side effect of systemic type.

Another object of the present invention is to provide a cosmetic compound in lotion for trichological use that is Easy to use and without high production costs.

In view of this goal, these objects and others which will be apparent later, a compound for topical application to reactivate the physiological growth of hair is provided, according to a first aspect of the invention, which comprises an association of cysteine, lysine and / or its derivatives with a glycoprotein in a physiologically acceptable vehicle.

Cysteine is an amino acid that contains sulfur whose presence in the biochemical process for the synthesis of Keratin is essential. Cysteine is indeed rich in -S-S- disulfidic bridges that constitute the link that holds together keratin polypeptide chains, which is A key protein in hair structure.

When applied locally, the cysteine that is present in the formulation according to the invention adheres in part to the keratin structure of the hair, strengthening your body, and is partially absorbed by the subcutaneous region of the scalp, thus helping to reduce and control increased sebaceous secretion of the scalp that often accompanies loss processes of hair.

Within the scope of the present invention, the term "cysteine derivative" means salts, esters or complexes with other physiologically acceptable substances.

A cysteine derivative particularly suitable is sodium lauroyl cysteine.

Lysine is an essential amino acid that promotes cell regeneration in the body and is an indispensable element for the physiological growth of the body. A lysine deficit of fact causes growth arrest, protein deficit and a reduction in the keratinization process.

The use of lysine or a derivative of yours in the formulation of the composition according to the invention has been tested fundamental at the level of the inner root sheath, to form lysine-glutamine linkages between chains polypeptides that help increase the substance and shape of the hair.

The expression "lysine derivative" is used in the description and in the claims to designate their salts, esters or complexes with other substances physiologically acceptable.

Within the scope of the present invention, a particularly suitable and active lysine derivative form is the lysine hydrochloride.

Surprisingly, it has now been discovered that the association of a glycoprotein, a molecule characterized by presence of a glycidic fraction and a protein fraction, with the active ingredients described above produces an effect synergistic about regrowth and hair structure.

The presence of the glycidic fraction in the molecule is believed to be essential in the formulation according to the invention because it increases cell cohesion by forming bridges intercellular and induces similar specific biological activities to hormonal and enzymatic activities.

It has been discovered that the addition of a cysteine glycoprotein and lysine greatly increases the utilization rate of the first two active ingredients in the Keratin biosynthesis.

Keratin is a substance that has a mass relatively high molecular, has a nature protein-fibrous and consists of a group of polypeptide chains originating from the condensation of amino acids. Keratin polypeptides are oriented so that are parallel to the longitudinal axis of the hair body and the  S-S- disulfidic bonds that form between two cysteine molecules are characteristic of the structure of the keratin

Local administration at the leather level lysine and cysteine scalp and / or its derivatives in association with a glycoprotein increases chain formation polypeptides, adding both sulfide bonds and amino acids, thus strengthening the keratin sheath and accordingly Strengthening the body of the hair.

Within the scope of the present invention, enter glycoproteins, it has been discovered that the lectin family It is particularly suitable for the preparation of a compound cosmetic-trichological.

Suitable lectins are both endogenous and exogenous in origin. The first are known as sarcolectins and they have an active role in the regulation of cell proliferation, particularly making cells sensitive to signs of increase. The latter are present in the tissues of the plants and can be extracted and purified easily.

According to a preferred embodiment of the invention, a lectin extracted from Solanum tuberosum L is used, which advantageously has a relative molecular mass of approximately 20,000 daltons. Lectin extraction and purification techniques are of a known type and are commonly used in the field of chemistry.

The inclusion of a glycoprotein in the formulation of a compound of the invention, particularly a lectin, produces a stimulation of cellular respiration that It leads to an activation of cellular metabolism processes.

It has now been unexpectedly seen that the association of said glycoprotein with cysteine and lysine or derivatives theirs produces a synergistic effect of the stimulation of hair growth that can be explained only partially by an increase in cellular respiration.

In particular, surprisingly it has discovered that the simultaneous administration of said three active ingredients causes an increase in oxygen consumption Regarding the baseline conditions. This increase unexpectedly large is combined with a considerable increase in the biosynthesis of Keratin structures of the hair.

The data obtained from in vitro assays carried out on human fibroblast cell lines and keratinocytes has produced more results, in terms of cell proliferation, which indicate a synergistic effect of the three base components of the compound according to the invention.

According to an embodiment example of the present invention, the cosmetic compound is in the form of a solution Water based suitable for topical application.

According to a preferred embodiment, the compound according to the invention comprises an additional active ingredient which is constituted by nicotinic acid or an ester thereof, conveniently the benzyl ester (benzyl nicotinate).

Topical application of an acid ester Nicotinic simultaneously with the three basic active ingredients of the formulation according to the invention produces local vasodilation with a temporary increase in blood flow at the capillary level, accompanied by a modest erythema and a slight increase in temperature.

In particular, the topical administration of benzyl nicotinate conveniently as a solution water-alcohol, increases the supply of oxygen and nutrients in the hair follicle level and increases your absorption by the hair bulb.

According to another embodiment, the compound for topical use according to the invention further includes a phospholipid, a highly fat-soluble molecule that acts as a vehicle active.

Phospholipids are ubiquitous molecules that are present in high concentrations at the membrane level cell and in endogenous lipoproteins and have an active role in various metabolic and biochemical processes, such as the oxidative cell phosphorylation, mitosis, ionic transport intra / extra cellular, chromosomatic replication and others.

In view of its structure, phospholipids they have a high affinity with the epithelial cell membrane, allowing the exchange and penetration of the principles active through said membrane.

The presence of a phospholipid in the formulation of the compound according to the invention, performs a dual action, acting as a vehicle of the active ingredients included and as an agent which facilitates its penetration through cell membranes.

A phospholipid that has been found particularly suitable for the application according to the present invention is phosphatidicoline, a derivative of lecithin, esterified with choline.

Phosphatidicoline is conveniently subjected to a preliminary treatment in order to increase its solubility in water and its stability in a water - alcohol solution, making it particularly suitable for the formulation of compounds according to the invention.

The preliminary treatment includes the mixture of three components: phosphatidicoline, butylene glycol and water, preferably at a temperature between 30 ° C and 50 ° C, more preferably at about 40 ° C, followed by cooling at room temperature of the resulting mixture, and by filtration this. According to a preferred embodiment, said three Components are mixed in the following weight ratios: 8 to 12% phosphatidicoline by weight; 40 to 60% butylene glycol by weight; 40 to 60% water by weight

Mixing step conveniently hard approximately 4 to 5 hours.

At the end of the treatment, a solution is obtained which is highly soluble in a water - alcohol solution with a percentage of ethyl alcohol generally between 50 and 60%.

Advantageously, this last solution is added, preferably in an amount equivalent to 0.05% by weight, to one of the compounds according to the invention.

An embodiment of the compound according to the invention comprises the following principles that are active in stimulate hair regrowth:

cysteine, lysine or its derivatives (hydrochloride of lysine and sodium lauroyl cysteine), glycoprotein (lectin), nicotinic acid ester (benzyl nicotinate) and phospholipid (phosphatidicoline).

Additional active ingredients that stimulate hair growth, advantageously selected from the group consisting of methionine and its derivatives, biotin, salicylate silanediol and mixtures thereof, can be incorporated into the compound of the present invention to further increase the stimulation of Hair growth.

The expression "methionine derivative" designates a salt and / or ester thereof with physiologically acceptable compounds. Zinc Acetyl Methionate is particularly suitable.

Biotin is preferably included in formulations of the compound according to the invention that are specific for the treatment of forms of alopecia that affect subjects Feminine

The compound for topical use according to the invention may also comprise additives conventionally used in Trichological preparations, such as preservatives, stabilizers, antibacterial agents, emulsifiers, buffers and colors. In in particular, when the compound is in solution form, preferably 0.04% by weight is added to a dye solution based on a brown dye or pigment. Said dye solution is performed by dissolving 50% water in a solution of aqueous base including 5% by weight of a dye or dye mixture Physiologically acceptable. Advantageously, said dye or pigment it's a mixture of CI 19140-14720-16255-73015-28440.

As a vehicle for the compound according to invention it is possible to use a solution water-alcohol that advantageously includes glycol and excipients commonly used in preparation techniques Cosmetics for local application.

As an example, it is possible to use as excipients glycerin, disodium EDTA, triethanolamine, menthol, benzophenone and physiologically acceptable vehicles and colors.

According to another aspect, the present invention provides a method for preparing a trichological compound, preferably in form of a solution (lotion), which comprises dissolving in water of water soluble fractions and the remaining fractions in a alcoholic solvent, followed by mixing the two fractions during mixing

The resulting mixture is then buffered with the in order to reach a pH range (between 6 and 6.8) that is compatible with the pH of the skin and is filtered and packaged in suitable containers, such as vials and bottles.

According to another aspect, the present invention makes in relation to the use of a synergistic trichological compound that it comprises a glycoprotein, cysteine and lysine and / or its derivatives to produce a preparation for stimulation of regrowth hair related.

The simultaneous use of these three principles assets produces a synergistic effect of stimulation of hair follicles that are not totally stunted, helping restore optimal physiological conditions for growth hair related.

The inclusion in the formulation of a room active ingredient that is constituted by nicotinic acid or a yours ester, such as benzyl nicotinate, is preferred.

The use according to this last aspect of the invention provides for the application of an effective cosmetic amount of compound according to the invention directly on the scalp, preferably once a day or on alternate days.

The compound can be applied locally, in the regions where hair is falling, one or more times at day, preferably following treatment cycles that last from two to three months alternated with a rest period.

According to another aspect of the present invention, a Cosmetic treatment method is provided that comprises the local application, at the level of the scalp, of an amount cosmetically effective of a compound of the type described previously.

The effectiveness in hair regrowth and in the local tolerability of a cited lotion compound in example 3 it has been evaluated clinically and through non-invasive instrumental research.

The treatment was carried out on the leather scalp of subjects affected by hair loss caused by forms of androgenic alopecia and / or defluvium and showed no effects secondary systemic type.

The treatment involved the application of a enough lotion to wet the leather surface scalp, advantageously on alternate days, during a period of preferably ninety days.

Instrumental measurements (sebum, hydration and pH) and clinical evaluations were carried out under conditions baseline one, two and three months after the beginning of treatment.

The following main parameters are They considered:

1) degree of alopecia and defluvium

2) degree of seborrhea in the scalp and in hair body

3) appearance of dandruff

4) tensile test.

In baseline conditions and at the end of treatment, the area of the skin subject to the electronic counting of the hair in the growth phase was shaved and photographed; An area affected by alopecia (hair insertion line along the right frontoparietal region) was photographed; and they took hair samples for morphological evaluation by optical microscope (bulb status, body condition, thickness and body brightness).

The study was carried out on a sample of 25 subjects, 14 women and 11 men, aged between 23 and 45 years, affected by grade I-II androgenetic alopecia according to Ludwig's scale for women and by the degree of Alopecia II-III according to the Hamilton scale for men, and / or defluvium.

Brief description of the drawings

The results obtained are summarized in the graphs shown in Figures 1 to 9, in which:

Figure 1 shows bar graphs of the average results of the tensile test carried out on the subjects treated. Four graphs are presented that relate to the baseline situation and condition after 1, 2, 3 months of treatment with the compound according to the invention;

Figure 2 shows bar graphs of the results found in the electronic hair count in baseline conditions and after treatment;

Figure 3 shows bar graphs of the mean values of the individual results outlined in the Figure 2;

Figure 4 shows bar graphs of the percentage variations in morphological conditions observed at the level of the hair bulb in the treated subjects, in the basal and final conditions;

Figure 5 is a bar graph of the percentage variations of the hair in a weakened form and form not weakened, at baseline conditions and after treatment;

Figure 6 is a bar chart of the average variation in the diameter of the hair of the subjects treated, at baseline and at the end of treatment;

Figure 7 is a bar chart of the average variation in the brightness of the hair of the treated subjects, in the basal condition and at the end of the treatment;

Figure 8 is a bar chart of the average variation in sebum measures of hair subjects treated in the baseline condition and after 1, 2, 3 months of treatment;

Figure 9 is a bar chart of the average variation of the hydration of the hair of the subjects treated, in the basal condition and after 1, 2, 3 months of treatment.

Ways of carrying out the invention

Figure 1 indicates that the cosmetic treatment induces a statistically significant reduction (P <0.05; test Bonferroni), equal to 33% of hair removed by the traction with respect to baseline, indicating an increase in tensile strength.

The data summarized in the graphs of the Figures 2 and 3 indicate that after a period of three months a statistically significant mean increase (P <0.001; Proof of t), equal to 13% of the baseline value in growing hair evaluated by electronic counting.

The electronic count of the number of hairs is carried out by shaving an area of the scalp located in the vertex and measuring 1 cm2. In order to identify subsequently shaving the same region without error in the different moments (1, 2, 3 months), an area with the help of a cardboard cutout, starting with three coordinates constituted by the end of the nose and the end of the ear pavilions. An electronic reference signal was set in the images obtained for electronic counting. This area is He photographed immediately after shaving and five days later. In this way it is possible to electronically count the hair in the active growth phase by image analysis computerized. Scanned images for electronic counting were achieved at times T0A and T3A for each subject individual to cosmetic treatment.

Figure 4 illustrates the morphological variations at the bulb level, observed by optical microscope. The Bulb analysis showed an increase in bulbs in the phase anagen, that is, in the growth phase of new hair (from 3.7 to 25.9% of total bulbs removed) and a reduction in the bulbs in the telogen phase (from 81.5% to 57.7% of the total bulbs extracted), which were statistically significant (P <0.05; T test).

Figure 5 shows the variations observed also at the level of the body of the hair following the treatment cosmetic according to the invention.

Variations in the bulb level and in the hair body diameter were determined by evaluation With an optical microscope.

First, a scalp region adjacent to the area of hair loss was selected. Then traction was applied until a sample composed of Approximately ten hairs were obtained. Hair samples extracted were collected in a transparent plastic bag. For microscopic analysis, the hairs were placed on a platen. If the hair was longer than the platen, the part of the hair protruding from said stage was cut and mounted on Another stage. A second stage was placed on the first and joined her with duct tape at its ends. The body was examined along its entire length with low magnification (x40) and with a major increase (x100 and x400), while examining the bulb and Extreme was carried out with a larger increase (x100 and x400). The following body characteristics were considered: state of the outer sheath, uniformity and ruptures of the body, if any. The characteristics of the bulb allowed to identify the phase of the hair (anagen, telogen). In the anagen phase, there is a final portion dark (the bulb) followed by a long dark central part (the body), surrounded by the inner root sheath. In the phase telogen, the final part of the body looks like a pad, the portion of the bulb is not pigmented and does not have the inner sheath of the root. The dystrophic bulb has a hook-shaped appearance or deformed and the pods may be absent, but keeps the pigmentation characteristics of the anagen phase and is the result of traction during hair removal.

Figure 6 shows that cosmetic treatment determines, in subjects treated for three months, an increase in hair diameter that is significant from the point of view cosmetic. In particular, the morphometric analysis of the hair has shown an average increase in diameter of 11.2% compared to basal conditions. Body thickness was measured by getting a enhanced computerized image of the hair.

Figure 7 shows that the brightness of the hair of the individuals subject to treatment do not present a variation particularly appreciable. In order to carry out the measurement brightness, parameter L according to the CIE standard (Commission Internationale de l'Eclairage L a b; 1976) was used as reference.

Figure 8 shows that after three months of treatment there is a modest reduction in the amount of sebum produced by the sebaceous glands of the scalp. Is reduction leads to an aesthetic improvement of the subject's hair treaty.

The Skin Analysis device (IMS, Haifa), constituted by an opaque glass surface mounted on a spring-loaded stage was used to determine the sebum values The measurement was carried out supporting the probe against the skin, by a constant pressure maintained by the spring-operated mechanism, for a few seconds and then returning the sensor to its seat. The device is thus capable of reading the photometric variation in surface transmittance dull after skin contact. The variation in Transparency of the probe surface is proportional to the increased lipids present on the surface of the skin. The value obtained on the device screen is inversely proportional to the amount of lipids collected by the probe.

The cosmetic treatment according to the invention determines a statistically significant increase (P> 0.05; test of Bonferroni) at the level of skin hydration, which is particularly evident when delineated as a bar chart (Figure 9).

The level of skin hydration was tested using a CM820 comeometer unit (Courage - Khazaka, Cologne, Germany) provided with a cylindrical sensor mounted on a spring-loaded stage capable of carrying out measurements capacitive electrical The measurements were carried out supporting the sensor on the skin with a constant pressure that can be get thanks to the spring-loaded stage. The measurement main is based on the fact that dielectric constants Water and other materials are very different. A condenser reacts with capacitance changes according to water content when tissue samples are placed within their volume of measurement. The measurement of the capacitive properties of the skin surface is therefore an indirect expression of its degree of hydration The value obtained on the screen of device is directly proportional to the water content in the skin surface

Example 1

Three types of compound formulation according to invention, particularly suitable for topical application to male subjects, are given below. The ingredients are provided by percentages by weight.

one

Example 2

Three types of compound formulation according to invention, particularly suitable for topical application to Female subjects, are given below. The ingredients are provided in percentages by weight.

two

Example 3

The activity of a preparation for topical application according to example 1 was subjected to evaluation clinic.

This research has been carried out to evaluate the effectiveness of the preparation to promote the physiological hair growth

A total of 10 men, aged between 34 and 44 years, affected by alopecia were selected and treated in double-blind conditions for 12 weeks A preparation containing the compound according to the invention was applied topically on a part (Side B) of the leather scalp, while on the other side (Side A) a lotion that did not contain such active ingredients.

Effectiveness was clinically evaluated by Controls carried out during and at the end of the investigation. All subjects showed a greater increase in growth in the part of the scalp treated with the product under examination. It should be noted that the action of the product under review takes place at the level of still active hair follicles.

The final evaluation carried out by the researcher for each test subject at the end of the treatment it is like follow:

3

Claims (13)

1. A cosmetic compound for topical application to reactivate the physiological growth of hair, comprising an association of cysteines or salts, esters or complexes of yours with other physiologically acceptable substances, lysines or salts, esters or complexes of yours with other substances physiologically acceptable and a glycoprotein, in a physiologically vehicle acceptable. 2. A compound according to claim 1, characterized in that said lysine derivative is lysine hydrochloride. 3. A compound according to claim 1 or 2, characterized in that said cysteine derivative is sodium lauroyl cysteine. 4. A compound according to any of claims 1 to 3, characterized in that said glycoprotein is a lectin. 5. A compound according to any of claims 1 to 4, characterized in that it further comprises a nicotinic acid ester. 6. A compound according to claim 5, characterized in that said nicotinic acid ester is benzyl nicotinate. 7. A compound according to any of claims 1 to 6, characterized in that it further comprises a phospholipid. 8. A compound according to claim 7, characterized in that said phospholipid is phosphatidicoline. 9. A compound according to any of claims 1 to 8, characterized in that it also comprises at least one of methionine or its derivatives, biotin, silanediol salicylate and mixtures thereof. 10. A compound according to any one of claims 1 to 9, characterized in that it is in the form of a water / alcohol based solution. 11. A compound according to any of claims 1 to 10, characterized in that it comprises the following active ingredients: 0.05 to 5% benzyl nicotinate by weight; 1 to 50% sodium lauroyl cysteine by weight; 0.05% to 40% lysine hydrochloride by weight; 1 to 50 parts per million glycoprotein; 0.001 to 1% phosphatidicoline by weight in a water / alcohol based vehicle. 12. A method of cosmetic treatment that includes topical application on the scalp of a cosmetically effective amount of a compound according to any of claims 1 to 11. 13. The use of a compound according to any of claims 1 to 11 for producing a cosmetic preparation for the treatment of forms of androgenic alopecia and / or defluvium